Department of Medicine, Division of Gastroenterology
Digestive System | Endocrine System Diseases | Endocrinology | Hormones, Hormone Substitutes, and Hormone Antagonists | Nutritional and Metabolic Diseases | Surgical Procedures, Operative
Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery; instead, we found that elevated plasma GLP-1 and PYY correlated with increased nutrient delivery to the distal gut in mice. We conclude that increased GLP-1 secretion after bariatric surgery arises from rapid nutrient delivery to the distal gut and is a key driver of enhanced insulin secretion.
GLP-1, bariatric surgery, enteroendocrine cells, gut hormones, intestinal transit, mass spectrometry, peptidomics, transcriptomics
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Copyright 2019 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
DOI of Published Version
Cell Rep. 2019 Feb 5;26(6):1399-1408.e6. doi: 10.1016/j.celrep.2019.01.047. Link to article on publisher's site
Larraufie, Pierre; Roberts, Geoffrey P.; McGavigan, Anne K.; Kay, Richard G.; Li, Joyce H.; Leiter, Andrew B.; Melvin, Audrey; Biggs, Emma K.; Ravn, Peter; Davy, Kathleen; Hornigold, David C.; Yeo, Giles S. H; Hardwick, Richard H.; Reimann, Frank; and Gribble, Fiona M., "Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery" (2019). Open Access Articles. 3770.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Digestive System Commons, Endocrine System Diseases Commons, Endocrinology Commons, Hormones, Hormone Substitutes, and Hormone Antagonists Commons, Nutritional and Metabolic Diseases Commons, Surgical Procedures, Operative Commons